Group IIA secreted phospholipase A(2) (group IIA sPLA(2)) is known to display potent Gram-positive bactericidal activity in vitro and in vivo. We have analyzed the bactericidal activity of the full set of native stingray and dromedary groups V, IIA, and IB sPLA(2)s on several Gram-positive and Gram-negative strains. The rank order potency among both marine and mammal sPLA(2)s against Gram-positive bacteria is group IIA > V > IB, whereas Gram-negative bacteria exhibited a much higher resistance. There is a synergic action of the sPLA(2) with lysozyme when added to the bacteria culture prior to sPLA(2).The bactericidal efficiency of groups V and IIA sPLA(2)s was shown to be dependent upon the presence of calcium ions and to a less extent Mg2+ ions and then a correlation could be made to its hydrolytic activity of membrane phospholipids. Importantly, we showed that stingray and dromedary groups V, IIA, and IB sPLA(2)s present no cytotoxicity after their incubation with MDA-MB-231cells. stingray groups V and IIA sPLA(2)s, like mammal ones, may be considered as future therapeutic agents against bacterial infections.